Enhanced antitumor efficacy by the combination of emodin and gemcitabine against human pancreatic cancer cells via downregulation of the expression of XIAP in vitro and in vivo

Sheng-Zhang Lin
2011 International Journal of Oncology  
XIAP and NF-κB play an important role in chemotherapy resistance in pancreatic cancer. The purpose of this study was to explore the role of XIAP and NF-κB in potentiating the antitumor effect of gemcitabine by emodin in pancreatic cancer. SW1990 cells were treated by sodium chloride, gemcitabine, emodin or their combination (gemcitabine plus emodin). Cellular proliferation and apoptosis were detected by Cell Counting kit-8 (CCK-8) assay and flow cytometry in vitro. The combination therapy more
more » ... ation therapy more significantly inhibited SW1990 cell growth and induced a higher percentage of apoptosis than monotherapy. Gemcitabine upregulated the expression of XIAP and NF-κB, while emodin or emodin plus gemcitabine downregulated them compared to the control group in vitro. SW1990 cells were used to establish orthotopic pancreatic tumor models in nude mice. Tumor-bearing mice were treated with sodium chloride, emodin, gemcitabine or their combination. After being treated for 4 weeks, the nude mice were imaged with high-resolution positron emission tomography (microPET) and fluorine-18-labeled fluorodeoxyglucose ( 18 F-FDG) to detect the tumor/non-tumor ratio (T/NT ratio) and standard uptake value (SUV). The mice were sacrificed to determine tumor weight. The combination of emodin and gemcitabine showed more significant reduction in the T/NT ratio, SUV and tumor weight compared to monotherapy. The mRNA levels and the protein expression of XIAP and NF-κB were upregulated in the gemcitabine group, while they were downregulated in the emodin group and the combination group in vivo. Ki-67 prolif eration index and TUNEL assay results also showed that emodin enhanced tumor apoptosis induced by gemcitabine in vivo. This study suggests that emodin enhances the antitumor effect of gemcitabine in SW1990 pancreatic cancer in vitro and in vivo, which may be via the downregulation of NF-κB expression, thus inhibiting the expression of XIAP.
doi:10.3892/ijo.2011.1115 pmid:21743963 fatcat:2z2kywqbbndmhgtvnlp55wraxu